Saethre-Chotzen syndrome

The autosomal-dominantly inherited Saethre-Chotzen syndrome (SCS) belongs to the family of craniosynostoses. The coronal suture is usually affected, resulting in brachycephaly or, in unilateral cases, plagiocephaly. A low forehead hairline, ptosis, hypertelorism and midface hypoplasia as well as small, posteriorly rotated auricles can often be observed. Brachydactyly and partial syndactyly, especially between fingers 2 and 3, as well as widened big toes, occasionally with splitting of the terminal phalanx, are sometimes seen. In most cases, mental development is not impaired. However, as with some other craniosynostosis syndromes, there is also a risk of increased intracranial pressure in SCS.

SCS is caused by causative changes in the TWIST1 gene, which codes for a transcription factor that is important for the development of mesodermal structures, among other things. Numerous different disease-causing variants have been found in the TWIST1 gene, including complete deletions. There is considerable variability, even within families among carriers of the same mutation.

Causative variants in the FGFR3, FGFR2 and TCF12 genes cause craniosynostosis syndromes that phenotypically overlap with SCS. The clinical overlap is particularly pronounced with Muenke syndrome.

References

Fitzpatrick 2013, Nat Genet 45:231 / Roscioli et al. 2013, Am J Med Genet C 163C:259 / Sharma et al. 2013, Nat Genet 45: 304 / Seto et al. 2007, Am J Med Genet 143A:678 / Kress et al. 2006, Eur J Hum Genet 14:39 / Chun et al. 2002, Am J Med Genet 110:136 / Chotzen 1932, Mschr Kinderheilk 55:97 / Saethre 1931, Dtsch Z Nervenheilk 119:533